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B-H⋯π and C-H⋯π interactions in protein-ligand complexes: carbonic anhydrase II inhibition by carborane sulfonamides.

Jindřich FanfrlíkJiří BryndaMichael KuglerMartin LepsikKlára PospíšilováJosef HolubDrahomír HnykJan NekvindaBohumir GrünerPavlína Řezáčová
Published in: Physical chemistry chemical physics : PCCP (2023)
Among non-covalent interactions, B-H⋯π and C-H⋯π hydrogen bonding is rather weak and less studied. Nevertheless, since both can affect the energetics of protein-ligand binding, their understanding is an important prerequisite for reliable predictions of affinities. Through a combination of high-resolution X-ray crystallography and quantum-chemical calculations on carbonic anhydrase II/carborane-based inhibitor systems, this paper provides the first example of B-H⋯π hydrogen bonding in a protein-ligand complex. It shows that the B-H⋯π interaction is stabilized by dispersion, followed by electrostatics. Furthermore, it demonstrates that the similar C-H⋯π interaction is twice as strong, with a slightly smaller contribution of dispersion and a slightly higher contribution of electrostatics. Such a detailed insight will facilitate the rational design of future protein ligands, controlling these types of non-covalent interactions.
Keyphrases
  • high resolution
  • protein protein
  • amino acid
  • binding protein
  • magnetic resonance imaging
  • mass spectrometry
  • magnetic resonance
  • molecular dynamics simulations
  • density functional theory
  • liquid chromatography